http://colil.dbcls.jp:18052/sparql?query=define%20sql%3Adescribe-mode%20%22CBD%22%20%20DESCRIBE%20%3Chttp%3A%2F%2Fpurl.jp%2Fbio%2F10%2Fcolil%2Fid%2F24633240%3E&output=application%2Fatom%2Bxml2024-03-29T15:32:41.367645ZOData Service and Descriptor DocumentnodeID://b5472663602024-03-29T15:32:41.367645Z2nodeID://b5472666332024-03-29T15:32:41.367645Z2nodeID://b5472667782024-03-29T15:32:41.367645Z2nodeID://b5472658782024-03-29T15:32:41.367645Z11nodeID://b5472660002024-03-29T15:32:41.367645Z4nodeID://b5472669062024-03-29T15:32:41.367645Z2nodeID://b5472661452024-03-29T15:32:41.367645Z3nodeID://b5472667912024-03-29T15:32:41.367645Z2nodeID://b5472664182024-03-29T15:32:41.367645Z2nodeID://b5472659122024-03-29T15:32:41.367645Z7nodeID://b5472668122024-03-29T15:32:41.367645Z2nodeID://b5472665762024-03-29T15:32:41.367645Z2nodeID://b5472669572024-03-29T15:32:41.367645Z2nodeID://b5472660512024-03-29T15:32:41.367645Z4nodeID://b5472663242024-03-29T15:32:41.367645Z2nodeID://b5472668492024-03-29T15:32:41.367645Z2nodeID://b5472659492024-03-29T15:32:41.367645Z5nodeID://b5472660882024-03-29T15:32:41.367645Z3nodeID://b5472669702024-03-29T15:32:41.367645Z2nodeID://b5472662162024-03-29T15:32:41.367645Z3nodeID://b5472664822024-03-29T15:32:41.367645Z2nodeID://b5472666102024-03-29T15:32:41.367645Z2nodeID://b5472667552024-03-29T15:32:41.367645Z2nodeID://b5472658552024-03-29T15:32:41.367645Z20nodeID://b5472661222024-03-29T15:32:41.367645Z3nodeID://b5472662672024-03-29T15:32:41.367645Z2nodeID://b5472666612024-03-29T15:32:41.367645Z2nodeID://b5472669342024-03-29T15:32:41.367645Z2nodeID://b5472661732024-03-29T15:32:41.367645Z3nodeID://b5472663012024-03-29T15:32:41.367645Z2nodeID://b5472664462024-03-29T15:32:41.367645Z2nodeID://b5472667192024-03-29T15:32:41.367645Z2nodeID://b5472659402024-03-29T15:32:41.367645Z6nodeID://b5472668402024-03-29T15:32:41.367645Z2nodeID://b5472669852024-03-29T15:32:41.367645Z2nodeID://b295389882024-03-29T15:32:41.367645ZThese anti-inflammatory properties, if exhibited by tumor-infiltrating macrophages, can provide a survival advantage to evolving tumors>>22<<,23. We thus examined the influence of human myeloid cells on tumor development in MI(S)TRG mice. We used the human melanoma cell line Me290 as a tumor model38. In agreement with clinical observations showing that myeloid cells infiltratenodeID://b5472663522024-03-29T15:32:41.367645Z2nodeID://b5472664972024-03-29T15:32:41.367645Z2nodeID://b5472666252024-03-29T15:32:41.367645Z2nodeID://b5472663892024-03-29T15:32:41.367645Z2nodeID://b5472659912024-03-29T15:32:41.367645Z4nodeID://b5472661372024-03-29T15:32:41.367645Z3nodeID://b5472667832024-03-29T15:32:41.367645Z2nodeID://b5472658832024-03-29T15:32:41.367645Z10nodeID://b5472660292024-03-29T15:32:41.367645Z4nodeID://b5472661502024-03-29T15:32:41.367645Z3nodeID://b5472665312024-03-29T15:32:41.367645Z2nodeID://b5472662952024-03-29T15:32:41.367645Z2nodeID://b5472664232024-03-29T15:32:41.367645Z2nodeID://b5472668042024-03-29T15:32:41.367645Z2nodeID://b5472659042024-03-29T15:32:41.367645Z8nodeID://b5472665682024-03-29T15:32:41.367645Z2nodeID://b5472669622024-03-29T15:32:41.367645Z2nodeID://b5472662082024-03-29T15:32:41.367645Z3nodeID://b5472664742024-03-29T15:32:41.367645Z2nodeID://b5472666022024-03-29T15:32:41.367645Z2nodeID://b5472667472024-03-29T15:32:41.367645Z2nodeID://b5472658472024-03-29T15:32:41.367645Z31nodeID://b5472661142024-03-29T15:32:41.367645Z3nodeID://b5472662592024-03-29T15:32:41.367645Z3nodeID://b5472663802024-03-29T15:32:41.367645Z2nodeID://b5472666532024-03-29T15:32:41.367645Z2nodeID://b5472658982024-03-29T15:32:41.367645Z9nodeID://b5472667982024-03-29T15:32:41.367645Z2nodeID://b5472660202024-03-29T15:32:41.367645Z4nodeID://b5472669262024-03-29T15:32:41.367645Z2nodeID://b5472661652024-03-29T15:32:41.367645Z3nodeID://b5472664382024-03-29T15:32:41.367645Z2nodeID://b5472659322024-03-29T15:32:41.367645Z6nodeID://b5472668322024-03-29T15:32:41.367645Z2nodeID://b5472665962024-03-29T15:32:41.367645Z2nodeID://b5472669772024-03-29T15:32:41.367645Z2nodeID://b5472660712024-03-29T15:32:41.367645Z4nodeID://b5472663442024-03-29T15:32:41.367645Z2nodeID://b5472668692024-03-29T15:32:41.367645Z2nodeID://b5472659692024-03-29T15:32:41.367645Z5nodeID://b5472669902024-03-29T15:32:41.367645Z2nodeID://b5472662362024-03-29T15:32:41.367645Z3nodeID://b5472666172024-03-29T15:32:41.367645Z2nodeID://b5472665092024-03-29T15:32:41.367645Z2nodeID://b5472666302024-03-29T15:32:41.367645Z2nodeID://b5472667752024-03-29T15:32:41.367645Z2nodeID://b5472658752024-03-29T15:32:41.367645Z12nodeID://b5472669032024-03-29T15:32:41.367645Z2nodeID://b5472661422024-03-29T15:32:41.367645Z3nodeID://b5472662872024-03-29T15:32:41.367645Z2nodeID://b5472664152024-03-29T15:32:41.367645Z2nodeID://b5472666812024-03-29T15:32:41.367645Z2nodeID://b5472669542024-03-29T15:32:41.367645Z2nodeID://b5472661932024-03-29T15:32:41.367645Z3nodeID://b5472663212024-03-29T15:32:41.367645Z2nodeID://b5472664662024-03-29T15:32:41.367645Z2nodeID://b5472667392024-03-29T15:32:41.367645Z2nodeID://b5472659602024-03-29T15:32:41.367645Z5nodeID://b5472668602024-03-29T15:32:41.367645Z2nodeID://b5472661062024-03-29T15:32:41.367645Z3nodeID://b5472670062024-03-29T15:32:41.367645Z2nodeID://b5472663722024-03-29T15:32:41.367645Z2nodeID://b5472665002024-03-29T15:32:41.367645Z2nodeID://b5472666452024-03-29T15:32:41.367645Z2nodeID://b5472660122024-03-29T15:32:41.367645Z4nodeID://b5472669182024-03-29T15:32:41.367645Z2nodeID://b5472661572024-03-29T15:32:41.367645Z3nodeID://b5472660492024-03-29T15:32:41.367645Z4nodeID://b5472669312024-03-29T15:32:41.367645Z2nodeID://b5472661702024-03-29T15:32:41.367645Z3nodeID://b5472659242024-03-29T15:32:41.367645Z7nodeID://b5472664432024-03-29T15:32:41.367645Z2nodeID://b5472668242024-03-29T15:32:41.367645Z2nodeID://b5472665882024-03-29T15:32:41.367645Z2nodeID://b5472667162024-03-29T15:32:41.367645Z2nodeID://b5472669822024-03-29T15:32:41.367645Z2nodeID://b5472662282024-03-29T15:32:41.367645Z3nodeID://b5472664942024-03-29T15:32:41.367645Z2nodeID://b5472666222024-03-29T15:32:41.367645Z2nodeID://b5472667672024-03-29T15:32:41.367645Z2nodeID://b5472658672024-03-29T15:32:41.367645Z14nodeID://b5472661342024-03-29T15:32:41.367645Z3nodeID://b5472662792024-03-29T15:32:41.367645Z2nodeID://b5472664072024-03-29T15:32:41.367645Z2nodeID://b5472666732024-03-29T15:32:41.367645Z2nodeID://b5472659012024-03-29T15:32:41.367645Z8nodeID://b5472668012024-03-29T15:32:41.367645Z2nodeID://b5472660402024-03-29T15:32:41.367645Z4nodeID://b5472669462024-03-29T15:32:41.367645Z2nodeID://b5472661852024-03-29T15:32:41.367645Z3nodeID://b5472663132024-03-29T15:32:41.367645Z2nodeID://b5472664582024-03-29T15:32:41.367645Z2nodeID://b5472659522024-03-29T15:32:41.367645Z5nodeID://b5472668522024-03-29T15:32:41.367645Z2nodeID://b5472664712024-03-29T15:32:41.367645Z2nodeID://b5472669972024-03-29T15:32:41.367645Z2nodeID://b5472659892024-03-29T15:32:41.367645Z5nodeID://b5472663642024-03-29T15:32:41.367645Z2nodeID://b5472668892024-03-29T15:32:41.367645Z2nodeID://b5472666372024-03-29T15:32:41.367645Z2nodeID://b5472662562024-03-29T15:32:41.367645Z3nodeID://b295390022024-03-29T15:32:41.367645Zpermit the study of low-proliferative, primary human hematopoietic malignancies, such as myelodysplastic syndromes or myeloproliferative neoplasia, that thus far have proven difficult to efficiently engraft [AR: OK] immunodeficient mice>>41<<,42.nodeID://b5472660042024-03-29T15:32:41.367645Z4nodeID://b5472665292024-03-29T15:32:41.367645Z2nodeID://b5472666502024-03-29T15:32:41.367645Z2nodeID://b5472667952024-03-29T15:32:41.367645Z2nodeID://b5472658952024-03-29T15:32:41.367645Z9nodeID://b295389692024-03-29T15:32:41.367645ZresultsnodeID://b5472669232024-03-29T15:32:41.367645Z2nodeID://b5472661622024-03-29T15:32:41.367645Z3nodeID://b5472664352024-03-29T15:32:41.367645Z2nodeID://b5472667082024-03-29T15:32:41.367645Z2nodeID://b5472669742024-03-29T15:32:41.367645Z2nodeID://b5472663412024-03-29T15:32:41.367645Z2nodeID://b5472664862024-03-29T15:32:41.367645Z2nodeID://b5472666142024-03-29T15:32:41.367645Z2nodeID://b5472667592024-03-29T15:32:41.367645Z2nodeID://b5472658592024-03-29T15:32:41.367645Z17nodeID://b5472668802024-03-29T15:32:41.367645Z2http://purl.jp/bio/10/colil/id/246332402024-03-29T15:32:41.367645Z10.1038%2Fnbt.2858PMC0nodeID://b5472659802024-03-29T15:32:41.367645Z5nodeID://b5472661262024-03-29T15:32:41.367645Z3nodeID://b5472663922024-03-29T15:32:41.367645Z2nodeID://b5472665202024-03-29T15:32:41.367645Z2nodeID://b5472666652024-03-29T15:32:41.367645Z2nodeID://b5472660322024-03-29T15:32:41.367645Z4nodeID://b5472669382024-03-29T15:32:41.367645Z2nodeID://b5472661772024-03-29T15:32:41.367645Z3nodeID://b5472663052024-03-29T15:32:41.367645Z2nodeID://b5472660692024-03-29T15:32:41.367645Z4nodeID://b5472669512024-03-29T15:32:41.367645Z2nodeID://b5472661902024-03-29T15:32:41.367645Z3nodeID://b5472659442024-03-29T15:32:41.367645Z6nodeID://b5472668442024-03-29T15:32:41.367645Z2nodeID://b5472664632024-03-29T15:32:41.367645Z2nodeID://b5472667362024-03-29T15:32:41.367645Z2nodeID://b5472662112024-03-29T15:32:41.367645Z3nodeID://b5472670032024-03-29T15:32:41.367645Z2nodeID://b5472661032024-03-29T15:32:41.367645Z3nodeID://b5472662482024-03-29T15:32:41.367645Z3nodeID://b5472666422024-03-29T15:32:41.367645Z2nodeID://b5472658872024-03-29T15:32:41.367645Z10nodeID://b5472667872024-03-29T15:32:41.367645Z2nodeID://b5472669152024-03-29T15:32:41.367645Z2nodeID://b295389812024-03-29T15:32:41.367645ZAs previously reported>>7<<,8,12, we observed very few human NK cells (hNKp46+hCD3-) in engrafted NSG mice (Fig.nodeID://b5472661542024-03-29T15:32:41.367645Z3nodeID://b5472662992024-03-29T15:32:41.367645Z2nodeID://b5472664272024-03-29T15:32:41.367645Z2nodeID://b5472666932024-03-29T15:32:41.367645Z2nodeID://b5472659212024-03-29T15:32:41.367645Z7nodeID://b5472668212024-03-29T15:32:41.367645Z2nodeID://b5472660602024-03-29T15:32:41.367645Z4nodeID://b5472669662024-03-29T15:32:41.367645Z2nodeID://b5472663332024-03-29T15:32:41.367645Z2nodeID://b5472664782024-03-29T15:32:41.367645Z2nodeID://b5472666062024-03-29T15:32:41.367645Z2nodeID://b5472659722024-03-29T15:32:41.367645Z5nodeID://b5472668722024-03-29T15:32:41.367645Z2nodeID://b5472664912024-03-29T15:32:41.367645Z2nodeID://b5472661182024-03-29T15:32:41.367645Z3nodeID://b5472663842024-03-29T15:32:41.367645Z2nodeID://b5472665122024-03-29T15:32:41.367645Z2nodeID://b5472666572024-03-29T15:32:41.367645Z2nodeID://b5472662762024-03-29T15:32:41.367645Z2nodeID://b295390042024-03-29T15:32:41.367645ZFor example, CD16+ monocytes, which develop in the MISTRG model but not in other humanized mouse models, are expanded in humans in inflammatory settings including those caused by HIV infection and atherosclerosis>>43<<. However, the functional significance of CD16+ monocytes in these settings is unknown; MI(S)TRG mice may enable the investigation of causal relationships between CD16+ monocytes and human inflammatory disease. Macrophages are alsonodeID://b5472660242024-03-29T15:32:41.367645Z4nodeID://b5472665492024-03-29T15:32:41.367645Z2nodeID://b5472666702024-03-29T15:32:41.367645Z2nodeID://b5472669432024-03-29T15:32:41.367645Z2nodeID://b5472661822024-03-29T15:32:41.367645Z3nodeID://b5472663102024-03-29T15:32:41.367645Z2nodeID://b5472664552024-03-29T15:32:41.367645Z2nodeID://b5472667282024-03-29T15:32:41.367645Z2nodeID://b5472669942024-03-29T15:32:41.367645Z2nodeID://b5472663612024-03-29T15:32:41.367645Z2nodeID://b5472666342024-03-29T15:32:41.367645Z2nodeID://b5472667792024-03-29T15:32:41.367645Z2nodeID://b5472658792024-03-29T15:32:41.367645Z11nodeID://b5472660012024-03-29T15:32:41.367645Z4nodeID://b5472669072024-03-29T15:32:41.367645Z2nodeID://b5472661462024-03-29T15:32:41.367645Z3nodeID://b5472664192024-03-29T15:32:41.367645Z2nodeID://b5472665402024-03-29T15:32:41.367645Z2nodeID://b5472666852024-03-29T15:32:41.367645Z2nodeID://b5472659132024-03-29T15:32:41.367645Z7nodeID://b5472668132024-03-29T15:32:41.367645Z2nodeID://b5472669582024-03-29T15:32:41.367645Z2nodeID://b5472660522024-03-29T15:32:41.367645Z4nodeID://b5472661972024-03-29T15:32:41.367645Z3nodeID://b5472663252024-03-29T15:32:41.367645Z2nodeID://b5472660892024-03-29T15:32:41.367645Z3nodeID://b5472669712024-03-29T15:32:41.367645Z2nodeID://b5472659642024-03-29T15:32:41.367645Z5nodeID://b5472668642024-03-29T15:32:41.367645Z2nodeID://b5472664832024-03-29T15:32:41.367645Z2nodeID://b5472667562024-03-29T15:32:41.367645Z2nodeID://b5472658562024-03-29T15:32:41.367645Z20nodeID://b5472662312024-03-29T15:32:41.367645Z3nodeID://b5472665042024-03-29T15:32:41.367645Z2nodeID://b5472661232024-03-29T15:32:41.367645Z3nodeID://b5472662682024-03-29T15:32:41.367645Z2nodeID://b5472666622024-03-29T15:32:41.367645Z2nodeID://b295389832024-03-29T15:32:41.367645ZAs previously reported7,8,>>12<<, we observed very few human NK cells (hNKp46+hCD3-) in engrafted NSG mice (Fig.nodeID://b5472669352024-03-29T15:32:41.367645Z2nodeID://b5472661742024-03-29T15:32:41.367645Z3nodeID://b5472663022024-03-29T15:32:41.367645Z2nodeID://b5472664472024-03-29T15:32:41.367645Z2nodeID://b5472659412024-03-29T15:32:41.367645Z6nodeID://b5472668412024-03-29T15:32:41.367645Z2nodeID://b5472660802024-03-29T15:32:41.367645Z3nodeID://b5472669862024-03-29T15:32:41.367645Z2nodeID://b5472663532024-03-29T15:32:41.367645Z2nodeID://b5472664982024-03-29T15:32:41.367645Z2nodeID://b5472666262024-03-29T15:32:41.367645Z2nodeID://b5472659922024-03-29T15:32:41.367645Z4nodeID://b5472668922024-03-29T15:32:41.367645Z2nodeID://b5472661382024-03-29T15:32:41.367645Z3nodeID://b5472667842024-03-29T15:32:41.367645Z2nodeID://b5472665322024-03-29T15:32:41.367645Z2nodeID://b5472666772024-03-29T15:32:41.367645Z2nodeID://b5472662962024-03-29T15:32:41.367645Z2nodeID://b5472668052024-03-29T15:32:41.367645Z2nodeID://b295389702024-03-29T15:32:41.367645ZNewborn MISTRG mice and their littermates MITRG (lacking the hSIRPA transgene) were sub-lethally irradiated and transplanted with human fetal liver-derived CD34+ cells, following a standard protocol>>27<< (see also Methods). Rag2-/-Il2rg-/- mice that share the same genetic background (129xBalb/c N2) but lack all the humanized alleles, and commercially available NOD-Scid Il2rg-/- (NSG) mice served as controls.nodeID://b295390062024-03-29T15:32:41.367645Zmonocyte-derived macrophages45, the trafficking of these cells in response to inflammation or infection, and the mechanisms of differentiation and effector function of M1 vs. M2 macrophages>>46<<.nodeID://b5472659052024-03-29T15:32:41.367645Z8nodeID://b5472660442024-03-29T15:32:41.367645Z4nodeID://b5472665692024-03-29T15:32:41.367645Z2nodeID://b5472666902024-03-29T15:32:41.367645Z2nodeID://b5472663172024-03-29T15:32:41.367645Z2nodeID://b5472669632024-03-29T15:32:41.367645Z2nodeID://b5472662092024-03-29T15:32:41.367645Z3nodeID://b5472663302024-03-29T15:32:41.367645Z2nodeID://b5472667112024-03-29T15:32:41.367645Z2nodeID://b5472664752024-03-29T15:32:41.367645Z2nodeID://b5472666032024-03-29T15:32:41.367645Z2nodeID://b5472667482024-03-29T15:32:41.367645Z2nodeID://b5472658482024-03-29T15:32:41.367645Z28nodeID://b5472661152024-03-29T15:32:41.367645Z3nodeID://b5472663812024-03-29T15:32:41.367645Z2nodeID://b5472666542024-03-29T15:32:41.367645Z2nodeID://b5472667992024-03-29T15:32:41.367645Z2nodeID://b5472658992024-03-29T15:32:41.367645Z9nodeID://b5472660212024-03-29T15:32:41.367645Z4nodeID://b5472669272024-03-29T15:32:41.367645Z2nodeID://b5472661662024-03-29T15:32:41.367645Z3nodeID://b5472664392024-03-29T15:32:41.367645Z2nodeID://b5472665602024-03-29T15:32:41.367645Z2nodeID://b5472668332024-03-29T15:32:41.367645Z2nodeID://b5472659332024-03-29T15:32:41.367645Z6nodeID://b5472660722024-03-29T15:32:41.367645Z4nodeID://b5472669782024-03-29T15:32:41.367645Z2nodeID://b5472662002024-03-29T15:32:41.367645Z3nodeID://b5472663452024-03-29T15:32:41.367645Z2nodeID://b5472669912024-03-29T15:32:41.367645Z2nodeID://b5472666182024-03-29T15:32:41.367645Z2nodeID://b5472659842024-03-29T15:32:41.367645Z5nodeID://b5472667762024-03-29T15:32:41.367645Z2nodeID://b5472658762024-03-29T15:32:41.367645Z12nodeID://b5472662512024-03-29T15:32:41.367645Z3nodeID://b5472665242024-03-29T15:32:41.367645Z2nodeID://b5472661432024-03-29T15:32:41.367645Z3nodeID://b5472662882024-03-29T15:32:41.367645Z2nodeID://b5472664162024-03-29T15:32:41.367645Z2nodeID://b5472666822024-03-29T15:32:41.367645Z2nodeID://b5472668102024-03-29T15:32:41.367645Z2nodeID://b5472659102024-03-29T15:32:41.367645Z7nodeID://b5472669552024-03-29T15:32:41.367645Z2nodeID://b295389852024-03-29T15:32:41.367645ZIt is not known which cell(s) are responsible for trans-presentation of IL-15 in vivo in humans; however, human myeloid cells can support human NK cell proliferation in vitro>>7<<. To test if trans-presentation of human IL-15 by human monocytes/macrophages underlies the improved human NK cell development in MISTRG mice, we treated MISTRG mice with liposome-encapsulated clodronate to deplete phagocytic cells.nodeID://b5472661942024-03-29T15:32:41.367645Z3nodeID://b5472663222024-03-29T15:32:41.367645Z2nodeID://b5472664672024-03-29T15:32:41.367645Z2nodeID://b5472659612024-03-29T15:32:41.367645Z5nodeID://b5472668612024-03-29T15:32:41.367645Z2nodeID://b5472661072024-03-29T15:32:41.367645Z3nodeID://b5472663732024-03-29T15:32:41.367645Z2nodeID://b5472665012024-03-29T15:32:41.367645Z2nodeID://b5472666462024-03-29T15:32:41.367645Z2nodeID://b5472660132024-03-29T15:32:41.367645Z4nodeID://b5472669192024-03-29T15:32:41.367645Z2nodeID://b5472661582024-03-29T15:32:41.367645Z3nodeID://b5472665522024-03-29T15:32:41.367645Z2nodeID://b5472666972024-03-29T15:32:41.367645Z2nodeID://b5472659252024-03-29T15:32:41.367645Z7nodeID://b5472668252024-03-29T15:32:41.367645Z2nodeID://b295389722024-03-29T15:32:41.367645Z1a) in NSG recipients was higher than in Rag2-/-Il2rg-/- recipients, as previously reported 28,>>30<<. The percentage of blood hCD45+ cells was similar in MISTRG, MITRG and in NSG, suggesting that the humanization of the four cytokine genes overcomes the need to induce phagocytic tolerance through SIRPα/CD47 cross-reactivity28,29,31,nodeID://b5472665892024-03-29T15:32:41.367645Z2nodeID://b5472660642024-03-29T15:32:41.367645Z4nodeID://b5472663372024-03-29T15:32:41.367645Z2nodeID://b5472669832024-03-29T15:32:41.367645Z2nodeID://b5472662292024-03-29T15:32:41.367645Z3nodeID://b5472667312024-03-29T15:32:41.367645Z2nodeID://b5472663502024-03-29T15:32:41.367645Z2nodeID://b5472664952024-03-29T15:32:41.367645Z2nodeID://b5472666232024-03-29T15:32:41.367645Z2nodeID://b5472667682024-03-29T15:32:41.367645Z2nodeID://b5472658682024-03-29T15:32:41.367645Z14nodeID://b5472661352024-03-29T15:32:41.367645Z3nodeID://b5472664082024-03-29T15:32:41.367645Z2nodeID://b5472666742024-03-29T15:32:41.367645Z2nodeID://b5472668022024-03-29T15:32:41.367645Z2nodeID://b5472659022024-03-29T15:32:41.367645Z8nodeID://b5472660412024-03-29T15:32:41.367645Z4nodeID://b5472669472024-03-29T15:32:41.367645Z2nodeID://b5472661862024-03-29T15:32:41.367645Z3nodeID://b5472663142024-03-29T15:32:41.367645Z2nodeID://b5472664592024-03-29T15:32:41.367645Z2nodeID://b5472665802024-03-29T15:32:41.367645Z2nodeID://b5472659532024-03-29T15:32:41.367645Z5nodeID://b5472668532024-03-29T15:32:41.367645Z2nodeID://b5472669982024-03-29T15:32:41.367645Z2nodeID://b5472660922024-03-29T15:32:41.367645Z3nodeID://b5472662202024-03-29T15:32:41.367645Z3nodeID://b5472663652024-03-29T15:32:41.367645Z2nodeID://b5472666382024-03-29T15:32:41.367645Z2nodeID://b5472660052024-03-29T15:32:41.367645Z4nodeID://b5472666512024-03-29T15:32:41.367645Z2nodeID://b5472667962024-03-29T15:32:41.367645Z2nodeID://b5472662712024-03-29T15:32:41.367645Z2nodeID://b5472658962024-03-29T15:32:41.367645Z9nodeID://b5472665442024-03-29T15:32:41.367645Z2nodeID://b5472661632024-03-29T15:32:41.367645Z3nodeID://b5472664362024-03-29T15:32:41.367645Z2nodeID://b5472668172024-03-29T15:32:41.367645Z2nodeID://b5472659172024-03-29T15:32:41.367645Z7nodeID://b5472667092024-03-29T15:32:41.367645Z2nodeID://b5472659302024-03-29T15:32:41.367645Z6nodeID://b5472668302024-03-29T15:32:41.367645Z2nodeID://b5472669752024-03-29T15:32:41.367645Z2nodeID://b295389872024-03-29T15:32:41.367645ZNK cells defend against pathogens by killing cells that lack surface MHC class I expression35, and by producing the IFN-γ >>36<<. Compared to human NK cells from NSG mice, NK cells from MISTRG mice expressed higher amounts of the lytic granule protein perforin (Fig. 5a-b) and exhibited significantly enhanced cytotoxic activity against human cells lacking MHC classnodeID://b5472663422024-03-29T15:32:41.367645Z2nodeID://b5472664872024-03-29T15:32:41.367645Z2nodeID://b5472666152024-03-29T15:32:41.367645Z2nodeID://b5472659812024-03-29T15:32:41.367645Z5nodeID://b5472668812024-03-29T15:32:41.367645Z2nodeID://b5472661272024-03-29T15:32:41.367645Z3nodeID://b5472663932024-03-29T15:32:41.367645Z2nodeID://b5472665212024-03-29T15:32:41.367645Z2nodeID://b5472666662024-03-29T15:32:41.367645Z2nodeID://b5472660332024-03-29T15:32:41.367645Z4nodeID://b5472669392024-03-29T15:32:41.367645Z2nodeID://b5472661782024-03-29T15:32:41.367645Z3nodeID://b5472663062024-03-29T15:32:41.367645Z2nodeID://b5472665722024-03-29T15:32:41.367645Z2nodeID://b5472661912024-03-29T15:32:41.367645Z3nodeID://b5472667002024-03-29T15:32:41.367645Z2nodeID://b5472659452024-03-29T15:32:41.367645Z5nodeID://b5472668452024-03-29T15:32:41.367645Z2nodeID://b295389742024-03-29T15:32:41.367645ZThe percentage of blood hCD45+ cells was similar in MISTRG, MITRG and in NSG, suggesting that the humanization of the four cytokine genes overcomes the need to induce phagocytic tolerance through SIRPα/CD47 cross-reactivity28,>>29<<,31, possibly due to defects in the mouse innate response caused by the absence of mouse cytokines.nodeID://b5472660842024-03-29T15:32:41.367645Z3nodeID://b5472662122024-03-29T15:32:41.367645Z3nodeID://b5472663572024-03-29T15:32:41.367645Z2nodeID://b5472662492024-03-29T15:32:41.367645Z3nodeID://b5472663702024-03-29T15:32:41.367645Z2nodeID://b5472658512024-03-29T15:32:41.367645Z24nodeID://b5472666432024-03-29T15:32:41.367645Z2nodeID://b5472667882024-03-29T15:32:41.367645Z2nodeID://b5472658882024-03-29T15:32:41.367645Z10nodeID://b5472660102024-03-29T15:32:41.367645Z4nodeID://b5472669162024-03-29T15:32:41.367645Z2nodeID://b5472661552024-03-29T15:32:41.367645Z3nodeID://b5472664282024-03-29T15:32:41.367645Z2nodeID://b5472659092024-03-29T15:32:41.367645Z7nodeID://b5472666942024-03-29T15:32:41.367645Z2nodeID://b5472659222024-03-29T15:32:41.367645Z7nodeID://b5472668222024-03-29T15:32:41.367645Z2nodeID://b5472660612024-03-29T15:32:41.367645Z4nodeID://b5472669672024-03-29T15:32:41.367645Z2nodeID://b5472663342024-03-29T15:32:41.367645Z2nodeID://b5472664792024-03-29T15:32:41.367645Z2nodeID://b5472666072024-03-29T15:32:41.367645Z2nodeID://b5472659732024-03-29T15:32:41.367645Z5nodeID://b5472668732024-03-29T15:32:41.367645Z2nodeID://b5472661192024-03-29T15:32:41.367645Z3nodeID://b5472662402024-03-29T15:32:41.367645Z3nodeID://b5472663852024-03-29T15:32:41.367645Z2nodeID://b5472665132024-03-29T15:32:41.367645Z2nodeID://b5472666582024-03-29T15:32:41.367645Z2nodeID://b5472660252024-03-29T15:32:41.367645Z4nodeID://b5472666712024-03-29T15:32:41.367645Z2nodeID://b5472661832024-03-29T15:32:41.367645Z3nodeID://b5472665642024-03-29T15:32:41.367645Z2nodeID://b5472659372024-03-29T15:32:41.367645Z6nodeID://b5472664562024-03-29T15:32:41.367645Z2nodeID://b5472668372024-03-29T15:32:41.367645Z2nodeID://b5472667292024-03-29T15:32:41.367645Z2nodeID://b5472662042024-03-29T15:32:41.367645Z3nodeID://b5472659502024-03-29T15:32:41.367645Z5nodeID://b5472668502024-03-29T15:32:41.367645Z2nodeID://b5472669952024-03-29T15:32:41.367645Z2nodeID://b295389892024-03-29T15:32:41.367645ZThese anti-inflammatory properties, if exhibited by tumor-infiltrating macrophages, can provide a survival advantage to evolving tumors22,>>23<<. We thus examined the influence of human myeloid cells on tumor development in MI(S)TRG mice. We used the human melanoma cell line Me290 as a tumor model38. In agreement with clinical observations showing that myeloid cells infiltratenodeID://b5472663622024-03-29T15:32:41.367645Z2nodeID://b5472666352024-03-29T15:32:41.367645Z2nodeID://b5472660022024-03-29T15:32:41.367645Z4nodeID://b5472669082024-03-29T15:32:41.367645Z2nodeID://b5472661472024-03-29T15:32:41.367645Z3nodeID://b5472665412024-03-29T15:32:41.367645Z2nodeID://b5472666862024-03-29T15:32:41.367645Z2nodeID://b5472659142024-03-29T15:32:41.367645Z7nodeID://b5472668142024-03-29T15:32:41.367645Z2nodeID://b5472660532024-03-29T15:32:41.367645Z4nodeID://b5472669592024-03-29T15:32:41.367645Z2nodeID://b5472661982024-03-29T15:32:41.367645Z3nodeID://b5472663262024-03-29T15:32:41.367645Z2nodeID://b5472665922024-03-29T15:32:41.367645Z2nodeID://b5472667202024-03-29T15:32:41.367645Z2nodeID://b295389762024-03-29T15:32:41.367645ZIn humans, three subsets of monocytes have been phenotypically and functionally described based on differential expression of CD14 and CD1619,>>32<< (CD14+CD16-, CD14+CD16+ and CD14dimCD16+). All three subpopulations were present in the blood as well as lymphoid and non-lymphoid tissues (e.g., lung and liver) of MI(S)TRG mice (Fig.nodeID://b5472668652024-03-29T15:32:41.367645Z2nodeID://b5472659652024-03-29T15:32:41.367645Z5nodeID://b5472662322024-03-29T15:32:41.367645Z3nodeID://b5472663772024-03-29T15:32:41.367645Z2nodeID://b5472665052024-03-29T15:32:41.367645Z2nodeID://b5472662692024-03-29T15:32:41.367645Z2nodeID://b5472663902024-03-29T15:32:41.367645Z2nodeID://b5472658712024-03-29T15:32:41.367645Z12nodeID://b5472660172024-03-29T15:32:41.367645Z4nodeID://b5472666632024-03-29T15:32:41.367645Z2nodeID://b5472660302024-03-29T15:32:41.367645Z4nodeID://b5472664112024-03-29T15:32:41.367645Z2nodeID://b5472669362024-03-29T15:32:41.367645Z2nodeID://b5472661752024-03-29T15:32:41.367645Z3nodeID://b5472663032024-03-29T15:32:41.367645Z2nodeID://b5472664482024-03-29T15:32:41.367645Z2nodeID://b5472659422024-03-29T15:32:41.367645Z6nodeID://b5472668422024-03-29T15:32:41.367645Z2nodeID://b5472660812024-03-29T15:32:41.367645Z3nodeID://b5472669872024-03-29T15:32:41.367645Z2nodeID://b5472663542024-03-29T15:32:41.367645Z2nodeID://b5472664992024-03-29T15:32:41.367645Z2nodeID://b5472666272024-03-29T15:32:41.367645Z2nodeID://b5472659932024-03-29T15:32:41.367645Z4nodeID://b5472668932024-03-29T15:32:41.367645Z2nodeID://b5472661392024-03-29T15:32:41.367645Z3nodeID://b5472662602024-03-29T15:32:41.367645Z3nodeID://b5472665332024-03-29T15:32:41.367645Z2nodeID://b5472666782024-03-29T15:32:41.367645Z2nodeID://b5472659062024-03-29T15:32:41.367645Z8nodeID://b5472668062024-03-29T15:32:41.367645Z2nodeID://b5472660452024-03-29T15:32:41.367645Z4nodeID://b5472666912024-03-29T15:32:41.367645Z2nodeID://b5472663182024-03-29T15:32:41.367645Z2nodeID://b5472669642024-03-29T15:32:41.367645Z2nodeID://b5472665842024-03-29T15:32:41.367645Z2nodeID://b5472667122024-03-29T15:32:41.367645Z2nodeID://b5472668572024-03-29T15:32:41.367645Z2nodeID://b5472664762024-03-29T15:32:41.367645Z2nodeID://b5472659572024-03-29T15:32:41.367645Z5nodeID://b5472667492024-03-29T15:32:41.367645Z2nodeID://b5472658492024-03-29T15:32:41.367645Z27nodeID://b5472662242024-03-29T15:32:41.367645Z3nodeID://b5472659702024-03-29T15:32:41.367645Z5nodeID://b5472668702024-03-29T15:32:41.367645Z2nodeID://b5472661162024-03-29T15:32:41.367645Z3nodeID://b5472663822024-03-29T15:32:41.367645Z2nodeID://b5472660092024-03-29T15:32:41.367645Z4nodeID://b5472665102024-03-29T15:32:41.367645Z2nodeID://b5472666552024-03-29T15:32:41.367645Z2nodeID://b5472660222024-03-29T15:32:41.367645Z4nodeID://b5472669282024-03-29T15:32:41.367645Z2nodeID://b5472661672024-03-29T15:32:41.367645Z3nodeID://b5472665612024-03-29T15:32:41.367645Z2nodeID://b5472659342024-03-29T15:32:41.367645Z6nodeID://b5472668342024-03-29T15:32:41.367645Z2nodeID://b5472660732024-03-29T15:32:41.367645Z4nodeID://b5472669792024-03-29T15:32:41.367645Z2nodeID://b5472662012024-03-29T15:32:41.367645Z3nodeID://b5472663462024-03-29T15:32:41.367645Z2nodeID://b5472666192024-03-29T15:32:41.367645Z2nodeID://b5472667402024-03-29T15:32:41.367645Z2nodeID://b5472659852024-03-29T15:32:41.367645Z5nodeID://b5472668852024-03-29T15:32:41.367645Z2nodeID://b295389782024-03-29T15:32:41.367645ZBased on these findings, we analyzed the development of human immune cells dependent on IL-15 trans-presentation, such as NK cells, in MI(S)TRG mice33,>>34<<. Efficient development of human NK cells in existing humanized mouse models requires injection of exogenous human IL-15/IL-15Rα 7,12; because mouse IL-15/IL15Rα is not sufficient to support human NK cells in vivo.nodeID://b5472662522024-03-29T15:32:41.367645Z3nodeID://b5472663972024-03-29T15:32:41.367645Z2nodeID://b5472665252024-03-29T15:32:41.367645Z2nodeID://b5472662892024-03-29T15:32:41.367645Z2nodeID://b5472658912024-03-29T15:32:41.367645Z9nodeID://b5472660372024-03-29T15:32:41.367645Z4nodeID://b5472666832024-03-29T15:32:41.367645Z2nodeID://b5472664312024-03-29T15:32:41.367645Z2nodeID://b5472660502024-03-29T15:32:41.367645Z4nodeID://b5472669562024-03-29T15:32:41.367645Z2nodeID://b5472661952024-03-29T15:32:41.367645Z3nodeID://b5472663232024-03-29T15:32:41.367645Z2nodeID://b5472667042024-03-29T15:32:41.367645Z2nodeID://b5472664682024-03-29T15:32:41.367645Z2nodeID://b5472659622024-03-29T15:32:41.367645Z5nodeID://b5472668622024-03-29T15:32:41.367645Z2nodeID://b5472661082024-03-29T15:32:41.367645Z3nodeID://b5472663742024-03-29T15:32:41.367645Z2nodeID://b5472665022024-03-29T15:32:41.367645Z2nodeID://b5472666472024-03-29T15:32:41.367645Z2nodeID://b5472660142024-03-29T15:32:41.367645Z4nodeID://b5472661592024-03-29T15:32:41.367645Z3nodeID://b5472662802024-03-29T15:32:41.367645Z2nodeID://b5472665532024-03-29T15:32:41.367645Z2nodeID://b5472666982024-03-29T15:32:41.367645Z2nodeID://b5472659262024-03-29T15:32:41.367645Z6nodeID://b5472668262024-03-29T15:32:41.367645Z2nodeID://b5472660652024-03-29T15:32:41.367645Z4nodeID://b5472663382024-03-29T15:32:41.367645Z2nodeID://b5472669842024-03-29T15:32:41.367645Z2nodeID://b5472667322024-03-29T15:32:41.367645Z2nodeID://b5472664962024-03-29T15:32:41.367645Z2nodeID://b5472668772024-03-29T15:32:41.367645Z2nodeID://b5472659772024-03-29T15:32:41.367645Z5nodeID://b295389902024-03-29T15:32:41.367645ZIn agreement with clinical observations showing that myeloid cells infiltrate tumors in several solid tumors>>23<<-26, we detected more human myeloid cell infiltration in tumors in MI(S)TRG than in NSG mice, as shown by the expression of human PTPRC mRNA (encodes CD45) and ITGAM mRNA (encodes CD11b) in subcutaneously grafted Me290 tumors (Fig.nodeID://b5472667692024-03-29T15:32:41.367645Z2nodeID://b5472662442024-03-29T15:32:41.367645Z3nodeID://b5472658692024-03-29T15:32:41.367645Z13nodeID://b5472668902024-03-29T15:32:41.367645Z2nodeID://b5472659902024-03-29T15:32:41.367645Z5nodeID://b5472661362024-03-29T15:32:41.367645Z3nodeID://b5472665172024-03-29T15:32:41.367645Z2nodeID://b5472664092024-03-29T15:32:41.367645Z2nodeID://b5472665302024-03-29T15:32:41.367645Z2nodeID://b5472669112024-03-29T15:32:41.367645Z2nodeID://b5472666752024-03-29T15:32:41.367645Z2nodeID://b5472668032024-03-29T15:32:41.367645Z2nodeID://b5472659032024-03-29T15:32:41.367645Z8nodeID://b5472660422024-03-29T15:32:41.367645Z4nodeID://b5472669482024-03-29T15:32:41.367645Z2nodeID://b5472661872024-03-29T15:32:41.367645Z3nodeID://b5472663152024-03-29T15:32:41.367645Z2nodeID://b5472665812024-03-29T15:32:41.367645Z2nodeID://b5472659542024-03-29T15:32:41.367645Z5nodeID://b5472668542024-03-29T15:32:41.367645Z2nodeID://b5472669992024-03-29T15:32:41.367645Z2nodeID://b5472660932024-03-29T15:32:41.367645Z3nodeID://b5472662212024-03-29T15:32:41.367645Z3nodeID://b5472663662024-03-29T15:32:41.367645Z2nodeID://b5472666392024-03-29T15:32:41.367645Z2nodeID://b5472658602024-03-29T15:32:41.367645Z16nodeID://b5472667602024-03-29T15:32:41.367645Z2nodeID://b5472660062024-03-29T15:32:41.367645Z4nodeID://b5472662722024-03-29T15:32:41.367645Z2nodeID://b5472664002024-03-29T15:32:41.367645Z2nodeID://b5472665452024-03-29T15:32:41.367645Z2nodeID://b5472668182024-03-29T15:32:41.367645Z2nodeID://b5472659182024-03-29T15:32:41.367645Z7nodeID://b5472660572024-03-29T15:32:41.367645Z4nodeID://b5472668312024-03-29T15:32:41.367645Z2nodeID://b5472664512024-03-29T15:32:41.367645Z2nodeID://b5472669762024-03-29T15:32:41.367645Z2nodeID://b5472660702024-03-29T15:32:41.367645Z4nodeID://b5472667242024-03-29T15:32:41.367645Z2nodeID://b5472663432024-03-29T15:32:41.367645Z2nodeID://b5472664882024-03-29T15:32:41.367645Z2nodeID://b5472666162024-03-29T15:32:41.367645Z2nodeID://b5472659822024-03-29T15:32:41.367645Z5nodeID://b295390002024-03-29T15:32:41.367645ZHuman NK cell cytotoxicity in vivo was determined following a previously reported protocol>>8<<. LCL721.221 (HLA class I negative) and LCL721.45 (HLA class I positive) cells were mixed in a 1:nodeID://b5472668822024-03-29T15:32:41.367645Z2nodeID://b5472661282024-03-29T15:32:41.367645Z3nodeID://b5472663942024-03-29T15:32:41.367645Z2nodeID://b5472665222024-03-29T15:32:41.367645Z2nodeID://b5472666672024-03-29T15:32:41.367645Z2nodeID://b5472660342024-03-29T15:32:41.367645Z4nodeID://b5472661792024-03-29T15:32:41.367645Z3nodeID://b5472663072024-03-29T15:32:41.367645Z2nodeID://b5472665732024-03-29T15:32:41.367645Z2nodeID://b5472667012024-03-29T15:32:41.367645Z2nodeID://b5472659462024-03-29T15:32:41.367645Z5nodeID://b5472668462024-03-29T15:32:41.367645Z2nodeID://b5472660852024-03-29T15:32:41.367645Z3nodeID://b5472662132024-03-29T15:32:41.367645Z3nodeID://b5472663582024-03-29T15:32:41.367645Z2nodeID://b5472658522024-03-29T15:32:41.367645Z22nodeID://b5472663712024-03-29T15:32:41.367645Z2nodeID://b5472667522024-03-29T15:32:41.367645Z2nodeID://b5472659972024-03-29T15:32:41.367645Z4nodeID://b5472668972024-03-29T15:32:41.367645Z2nodeID://b295389922024-03-29T15:32:41.367645ZVEGF is one such molecule39,>>40<<, and to test whether it was involved in tumor growth in MISTRG mice, we treated the mice with the human-VEGF inhibitor Avastin™.nodeID://b5472667892024-03-29T15:32:41.367645Z2nodeID://b5472658892024-03-29T15:32:41.367645Z9nodeID://b5472662642024-03-29T15:32:41.367645Z2nodeID://b5472661562024-03-29T15:32:41.367645Z3nodeID://b5472665372024-03-29T15:32:41.367645Z2nodeID://b5472664292024-03-29T15:32:41.367645Z2nodeID://b5472665502024-03-29T15:32:41.367645Z2nodeID://b5472666952024-03-29T15:32:41.367645Z2nodeID://b5472668232024-03-29T15:32:41.367645Z2nodeID://b5472659232024-03-29T15:32:41.367645Z7nodeID://b5472660622024-03-29T15:32:41.367645Z4nodeID://b5472669682024-03-29T15:32:41.367645Z2nodeID://b5472663352024-03-29T15:32:41.367645Z2nodeID://b5472666082024-03-29T15:32:41.367645Z2nodeID://b5472659742024-03-29T15:32:41.367645Z5nodeID://b5472668742024-03-29T15:32:41.367645Z2nodeID://b5472662412024-03-29T15:32:41.367645Z3nodeID://b5472663862024-03-29T15:32:41.367645Z2nodeID://b5472665142024-03-29T15:32:41.367645Z2nodeID://b5472666592024-03-29T15:32:41.367645Z2nodeID://b5472667802024-03-29T15:32:41.367645Z2nodeID://b5472658802024-03-29T15:32:41.367645Z11nodeID://b5472660262024-03-29T15:32:41.367645Z4nodeID://b5472662922024-03-29T15:32:41.367645Z2nodeID://b5472664202024-03-29T15:32:41.367645Z2nodeID://b5472665652024-03-29T15:32:41.367645Z2nodeID://b5472659382024-03-29T15:32:41.367645Z6nodeID://b5472668382024-03-29T15:32:41.367645Z2nodeID://b5472660772024-03-29T15:32:41.367645Z4nodeID://b5472662052024-03-29T15:32:41.367645Z3nodeID://b5472668512024-03-29T15:32:41.367645Z2nodeID://b5472660902024-03-29T15:32:41.367645Z3nodeID://b5472669962024-03-29T15:32:41.367645Z2nodeID://b5472667442024-03-29T15:32:41.367645Z2nodeID://b5472663632024-03-29T15:32:41.367645Z2nodeID://b5472666362024-03-29T15:32:41.367645Z2nodeID://b5472661112024-03-29T15:32:41.367645Z3nodeID://b5472660032024-03-29T15:32:41.367645Z4nodeID://b5472669092024-03-29T15:32:41.367645Z2nodeID://b5472661482024-03-29T15:32:41.367645Z3nodeID://b5472665422024-03-29T15:32:41.367645Z2nodeID://b5472666872024-03-29T15:32:41.367645Z2nodeID://b5472668152024-03-29T15:32:41.367645Z2nodeID://b295389712024-03-29T15:32:41.367645Z1a) in NSG recipients was higher than in Rag2-/-Il2rg-/- recipients, as previously reported >>28<<,30. The percentage of blood hCD45+ cells was similar in MISTRG, MITRG and in NSG, suggesting that the humanization of the four cytokine genes overcomes the need to induce phagocytic tolerance through SIRPα/CD47 cross-reactivity28,29,31,nodeID://b5472659152024-03-29T15:32:41.367645Z7nodeID://b5472660542024-03-29T15:32:41.367645Z4nodeID://b5472661992024-03-29T15:32:41.367645Z3nodeID://b5472663272024-03-29T15:32:41.367645Z2nodeID://b5472665932024-03-29T15:32:41.367645Z2nodeID://b5472667212024-03-29T15:32:41.367645Z2nodeID://b5472659662024-03-29T15:32:41.367645Z5nodeID://b5472668662024-03-29T15:32:41.367645Z2nodeID://b5472662332024-03-29T15:32:41.367645Z3nodeID://b5472663782024-03-29T15:32:41.367645Z2nodeID://b5472665062024-03-29T15:32:41.367645Z2nodeID://b5472667722024-03-29T15:32:41.367645Z2nodeID://b5472658722024-03-29T15:32:41.367645Z12nodeID://b5472663912024-03-29T15:32:41.367645Z2nodeID://b5472660182024-03-29T15:32:41.367645Z4nodeID://b5472669002024-03-29T15:32:41.367645Z2nodeID://b295389942024-03-29T15:32:41.367645Zcodon) of individual loci (encoding TPO, IL-3/GM-CSF or M-CSF) in the Rag2-/- Il2rg-/- 129xBalb/c (N2) genetic background was performed using Velocigene Technology in collaboration with Regeneron Pharmaceuticals, as reported previously>>16<<-18. Human SIRPα expression was achieved by BAC-transgenesis in the same genetic background28.nodeID://b5472662842024-03-29T15:32:41.367645Z2nodeID://b5472664122024-03-29T15:32:41.367645Z2nodeID://b5472665572024-03-29T15:32:41.367645Z2nodeID://b5472661762024-03-29T15:32:41.367645Z3nodeID://b5472664492024-03-29T15:32:41.367645Z2nodeID://b5472665702024-03-29T15:32:41.367645Z2nodeID://b5472659432024-03-29T15:32:41.367645Z6nodeID://b5472668432024-03-29T15:32:41.367645Z2nodeID://b5472669882024-03-29T15:32:41.367645Z2nodeID://b5472660822024-03-29T15:32:41.367645Z3nodeID://b5472662102024-03-29T15:32:41.367645Z3nodeID://b5472663552024-03-29T15:32:41.367645Z2nodeID://b5472666282024-03-29T15:32:41.367645Z2nodeID://b5472659942024-03-29T15:32:41.367645Z4nodeID://b5472668942024-03-29T15:32:41.367645Z2nodeID://b5472662612024-03-29T15:32:41.367645Z3nodeID://b5472665342024-03-29T15:32:41.367645Z2nodeID://b5472666792024-03-29T15:32:41.367645Z2nodeID://b5472659072024-03-29T15:32:41.367645Z7nodeID://b5472668072024-03-29T15:32:41.367645Z2nodeID://b5472660462024-03-29T15:32:41.367645Z4nodeID://b5472663192024-03-29T15:32:41.367645Z2nodeID://b5472664402024-03-29T15:32:41.367645Z2nodeID://b5472665852024-03-29T15:32:41.367645Z2nodeID://b5472667132024-03-29T15:32:41.367645Z2nodeID://b5472659582024-03-29T15:32:41.367645Z5nodeID://b5472668582024-03-29T15:32:41.367645Z2nodeID://b5472660972024-03-29T15:32:41.367645Z3nodeID://b5472662252024-03-29T15:32:41.367645Z3nodeID://b5472668712024-03-29T15:32:41.367645Z2nodeID://b5472663832024-03-29T15:32:41.367645Z2nodeID://b5472667642024-03-29T15:32:41.367645Z2nodeID://b5472658642024-03-29T15:32:41.367645Z15nodeID://b5472666562024-03-29T15:32:41.367645Z2nodeID://b5472661312024-03-29T15:32:41.367645Z3nodeID://b5472660232024-03-29T15:32:41.367645Z4nodeID://b5472669292024-03-29T15:32:41.367645Z2nodeID://b5472664042024-03-29T15:32:41.367645Z2nodeID://b5472661682024-03-29T15:32:41.367645Z3nodeID://b5472665622024-03-29T15:32:41.367645Z2nodeID://b5472659352024-03-29T15:32:41.367645Z6nodeID://b5472668352024-03-29T15:32:41.367645Z2nodeID://b295389732024-03-29T15:32:41.367645ZThe percentage of blood hCD45+ cells was similar in MISTRG, MITRG and in NSG, suggesting that the humanization of the four cytokine genes overcomes the need to induce phagocytic tolerance through SIRPα/CD47 cross-reactivity>>28<<,29,31, possibly due to defects in the mouse innate response caused by the absence of mouse cytokines.nodeID://b5472660742024-03-29T15:32:41.367645Z4nodeID://b5472662022024-03-29T15:32:41.367645Z3nodeID://b5472663472024-03-29T15:32:41.367645Z2nodeID://b5472667412024-03-29T15:32:41.367645Z2nodeID://b5472659862024-03-29T15:32:41.367645Z5nodeID://b5472668862024-03-29T15:32:41.367645Z2nodeID://b5472662532024-03-29T15:32:41.367645Z3nodeID://b5472663982024-03-29T15:32:41.367645Z2nodeID://b5472665262024-03-29T15:32:41.367645Z2nodeID://b5472667922024-03-29T15:32:41.367645Z2nodeID://b5472658922024-03-29T15:32:41.367645Z9nodeID://b5472660382024-03-29T15:32:41.367645Z4nodeID://b5472669202024-03-29T15:32:41.367645Z2nodeID://b295389962024-03-29T15:32:41.367645ZRecipient mice were engrafted with human hematopoietic stem and progenitor cells as previously described>>16<<-18,27,28. Briefly, human fetal liver samples were cut in small fragments, treated for 45 min at 37°C with Collagenase D (Roche, 100 ng/mL) and a cell suspension was prepared.nodeID://b5472666842024-03-29T15:32:41.367645Z2nodeID://b5472664322024-03-29T15:32:41.367645Z2nodeID://b5472665772024-03-29T15:32:41.367645Z2nodeID://b5472661962024-03-29T15:32:41.367645Z3nodeID://b5472667052024-03-29T15:32:41.367645Z2nodeID://b5472664692024-03-29T15:32:41.367645Z2nodeID://b5472665902024-03-29T15:32:41.367645Z2nodeID://b5472662172024-03-29T15:32:41.367645Z3nodeID://b5472659632024-03-29T15:32:41.367645Z5nodeID://b5472668632024-03-29T15:32:41.367645Z2nodeID://b5472661092024-03-29T15:32:41.367645Z3nodeID://b5472662302024-03-29T15:32:41.367645Z3nodeID://b5472666112024-03-29T15:32:41.367645Z2nodeID://b5472663752024-03-29T15:32:41.367645Z2nodeID://b5472665032024-03-29T15:32:41.367645Z2nodeID://b5472666482024-03-29T15:32:41.367645Z2nodeID://b5472660152024-03-29T15:32:41.367645Z4nodeID://b5472662812024-03-29T15:32:41.367645Z2nodeID://b5472665542024-03-29T15:32:41.367645Z2nodeID://b5472666992024-03-29T15:32:41.367645Z2nodeID://b5472659272024-03-29T15:32:41.367645Z6nodeID://b5472668272024-03-29T15:32:41.367645Z2nodeID://b5472660662024-03-29T15:32:41.367645Z4nodeID://b5472663392024-03-29T15:32:41.367645Z2nodeID://b5472664602024-03-29T15:32:41.367645Z2nodeID://b5472667332024-03-29T15:32:41.367645Z2nodeID://b5472659782024-03-29T15:32:41.367645Z5nodeID://b5472668782024-03-29T15:32:41.367645Z2nodeID://b5472670002024-03-29T15:32:41.367645Z2nodeID://b5472661002024-03-29T15:32:41.367645Z3nodeID://b5472662452024-03-29T15:32:41.367645Z3nodeID://b5472668912024-03-29T15:32:41.367645Z2nodeID://b5472665182024-03-29T15:32:41.367645Z2nodeID://b5472658842024-03-29T15:32:41.367645Z10nodeID://b5472669122024-03-29T15:32:41.367645Z2nodeID://b5472666762024-03-29T15:32:41.367645Z2nodeID://b5472661512024-03-29T15:32:41.367645Z3nodeID://b5472664242024-03-29T15:32:41.367645Z2nodeID://b5472669492024-03-29T15:32:41.367645Z2nodeID://b5472660432024-03-29T15:32:41.367645Z4nodeID://b5472661882024-03-29T15:32:41.367645Z3nodeID://b5472663162024-03-29T15:32:41.367645Z2nodeID://b5472665822024-03-29T15:32:41.367645Z2nodeID://b5472667102024-03-29T15:32:41.367645Z2nodeID://b5472659552024-03-29T15:32:41.367645Z5nodeID://b5472668552024-03-29T15:32:41.367645Z2nodeID://b295389752024-03-29T15:32:41.367645ZThe percentage of blood hCD45+ cells was similar in MISTRG, MITRG and in NSG, suggesting that the humanization of the four cytokine genes overcomes the need to induce phagocytic tolerance through SIRPα/CD47 cross-reactivity28,29,>>31<<, possibly due to defects in the mouse innate response caused by the absence of mouse cytokines.nodeID://b5472660942024-03-29T15:32:41.367645Z3nodeID://b5472662222024-03-29T15:32:41.367645Z3nodeID://b5472663672024-03-29T15:32:41.367645Z2nodeID://b5472667612024-03-29T15:32:41.367645Z2nodeID://b5472658612024-03-29T15:32:41.367645Z16nodeID://b5472660072024-03-29T15:32:41.367645Z4nodeID://b5472662732024-03-29T15:32:41.367645Z2nodeID://b5472664012024-03-29T15:32:41.367645Z2nodeID://b5472665462024-03-29T15:32:41.367645Z2nodeID://b5472659192024-03-29T15:32:41.367645Z7nodeID://b5472668192024-03-29T15:32:41.367645Z2nodeID://b5472669402024-03-29T15:32:41.367645Z2nodeID://b5472660582024-03-29T15:32:41.367645Z4nodeID://b295389982024-03-29T15:32:41.367645ZRecipient mice were engrafted with human hematopoietic stem and progenitor cells as previously described16-18,27,>>28<<. Briefly, human fetal liver samples were cut in small fragments, treated for 45 min at 37°C with Collagenase D (Roche, 100 ng/mL) and a cell suspension was prepared.nodeID://b5472664522024-03-29T15:32:41.367645Z2nodeID://b5472665972024-03-29T15:32:41.367645Z2nodeID://b5472667252024-03-29T15:32:41.367645Z2nodeID://b5472664892024-03-29T15:32:41.367645Z2nodeID://b5472662372024-03-29T15:32:41.367645Z3nodeID://b5472659832024-03-29T15:32:41.367645Z5nodeID://b5472668832024-03-29T15:32:41.367645Z2nodeID://b5472661292024-03-29T15:32:41.367645Z3nodeID://b5472666312024-03-29T15:32:41.367645Z2nodeID://b5472662502024-03-29T15:32:41.367645Z3nodeID://b5472663952024-03-29T15:32:41.367645Z2nodeID://b5472665232024-03-29T15:32:41.367645Z2nodeID://b5472669042024-03-29T15:32:41.367645Z2nodeID://b5472666682024-03-29T15:32:41.367645Z2nodeID://b5472660352024-03-29T15:32:41.367645Z4nodeID://b5472663082024-03-29T15:32:41.367645Z2nodeID://b5472665742024-03-29T15:32:41.367645Z2nodeID://b5472667022024-03-29T15:32:41.367645Z2nodeID://b5472659472024-03-29T15:32:41.367645Z5nodeID://b5472668472024-03-29T15:32:41.367645Z2nodeID://b5472660862024-03-29T15:32:41.367645Z3nodeID://b5472662142024-03-29T15:32:41.367645Z3nodeID://b5472663592024-03-29T15:32:41.367645Z2nodeID://b5472664802024-03-29T15:32:41.367645Z2nodeID://b5472667532024-03-29T15:32:41.367645Z2nodeID://b5472658532024-03-29T15:32:41.367645Z22nodeID://b5472659982024-03-29T15:32:41.367645Z4nodeID://b5472668982024-03-29T15:32:41.367645Z2nodeID://b5472661202024-03-29T15:32:41.367645Z3nodeID://b5472662652024-03-29T15:32:41.367645Z2nodeID://b5472665382024-03-29T15:32:41.367645Z2nodeID://b5472669322024-03-29T15:32:41.367645Z2nodeID://b5472665512024-03-29T15:32:41.367645Z2nodeID://b5472666962024-03-29T15:32:41.367645Z2nodeID://b5472661712024-03-29T15:32:41.367645Z3nodeID://b5472664442024-03-29T15:32:41.367645Z2nodeID://b5472660632024-03-29T15:32:41.367645Z4nodeID://b5472669692024-03-29T15:32:41.367645Z2nodeID://b5472663362024-03-29T15:32:41.367645Z2nodeID://b5472667172024-03-29T15:32:41.367645Z2nodeID://b5472666092024-03-29T15:32:41.367645Z2nodeID://b5472667302024-03-29T15:32:41.367645Z2nodeID://b5472668752024-03-29T15:32:41.367645Z2nodeID://b295389772024-03-29T15:32:41.367645Z3c), reflecting the physiological properties of the corresponding subpopulations in human blood>>32<<. After injection with LPS or infection with Listeria monocytogenes or influenza A we detected higher amounts of human TNFα, IL-6 and interferon-β (IFNβ) in the tissues of MI(S)TRG compared to NSG mice (Fig. 3d-f). These resultsnodeID://b5472659752024-03-29T15:32:41.367645Z5nodeID://b5472662422024-03-29T15:32:41.367645Z3nodeID://b5472663872024-03-29T15:32:41.367645Z2nodeID://b5472665152024-03-29T15:32:41.367645Z2nodeID://b5472667812024-03-29T15:32:41.367645Z2nodeID://b5472658812024-03-29T15:32:41.367645Z11nodeID://b5472660272024-03-29T15:32:41.367645Z4nodeID://b5472662932024-03-29T15:32:41.367645Z2nodeID://b5472664212024-03-29T15:32:41.367645Z2nodeID://b5472665662024-03-29T15:32:41.367645Z2nodeID://b5472659392024-03-29T15:32:41.367645Z6nodeID://b5472668392024-03-29T15:32:41.367645Z2nodeID://b5472660782024-03-29T15:32:41.367645Z4nodeID://b5472669602024-03-29T15:32:41.367645Z2nodeID://b5472662062024-03-29T15:32:41.367645Z3nodeID://b5472664722024-03-29T15:32:41.367645Z2nodeID://b5472660912024-03-29T15:32:41.367645Z3nodeID://b5472666002024-03-29T15:32:41.367645Z2nodeID://b5472667452024-03-29T15:32:41.367645Z2nodeID://b5472661122024-03-29T15:32:41.367645Z3nodeID://b5472662572024-03-29T15:32:41.367645Z3nodeID://b5472661492024-03-29T15:32:41.367645Z3nodeID://b5472662702024-03-29T15:32:41.367645Z2nodeID://b5472665432024-03-29T15:32:41.367645Z2nodeID://b5472669242024-03-29T15:32:41.367645Z2nodeID://b5472666882024-03-29T15:32:41.367645Z2nodeID://b5472659162024-03-29T15:32:41.367645Z7nodeID://b5472668162024-03-29T15:32:41.367645Z2nodeID://b5472660552024-03-29T15:32:41.367645Z4nodeID://b5472663282024-03-29T15:32:41.367645Z2nodeID://b5472665942024-03-29T15:32:41.367645Z2nodeID://b5472667222024-03-29T15:32:41.367645Z2nodeID://b5472659672024-03-29T15:32:41.367645Z5nodeID://b5472668672024-03-29T15:32:41.367645Z2nodeID://b5472662342024-03-29T15:32:41.367645Z3nodeID://b5472663792024-03-29T15:32:41.367645Z2nodeID://b5472665072024-03-29T15:32:41.367645Z2nodeID://b5472658732024-03-29T15:32:41.367645Z12nodeID://b5472667732024-03-29T15:32:41.367645Z2nodeID://b5472660192024-03-29T15:32:41.367645Z4nodeID://b5472669012024-03-29T15:32:41.367645Z2nodeID://b5472661402024-03-29T15:32:41.367645Z3nodeID://b5472662852024-03-29T15:32:41.367645Z2nodeID://b5472664132024-03-29T15:32:41.367645Z2nodeID://b5472665582024-03-29T15:32:41.367645Z2nodeID://b5472665712024-03-29T15:32:41.367645Z2nodeID://b5472669522024-03-29T15:32:41.367645Z2nodeID://b5472660832024-03-29T15:32:41.367645Z3nodeID://b5472669892024-03-29T15:32:41.367645Z2nodeID://b5472664642024-03-29T15:32:41.367645Z2nodeID://b5472667372024-03-29T15:32:41.367645Z2nodeID://b5472663562024-03-29T15:32:41.367645Z2nodeID://b5472666292024-03-29T15:32:41.367645Z2nodeID://b5472670042024-03-29T15:32:41.367645Z2nodeID://b5472661042024-03-29T15:32:41.367645Z3nodeID://b5472667502024-03-29T15:32:41.367645Z2nodeID://b5472658502024-03-29T15:32:41.367645Z27nodeID://b5472659952024-03-29T15:32:41.367645Z4nodeID://b295389792024-03-29T15:32:41.367645ZEfficient development of human NK cells in existing humanized mouse models requires injection of exogenous human IL-15/IL-15Rα >>7<<,12; because mouse IL-15/IL15Rα is not sufficient to support human NK cells in vivo.nodeID://b5472668952024-03-29T15:32:41.367645Z2nodeID://b5472662622024-03-29T15:32:41.367645Z3nodeID://b5472665352024-03-29T15:32:41.367645Z2nodeID://b5472668082024-03-29T15:32:41.367645Z2nodeID://b5472659082024-03-29T15:32:41.367645Z7nodeID://b5472660472024-03-29T15:32:41.367645Z4nodeID://b5472664412024-03-29T15:32:41.367645Z2nodeID://b5472665862024-03-29T15:32:41.367645Z2nodeID://b5472667142024-03-29T15:32:41.367645Z2nodeID://b5472659592024-03-29T15:32:41.367645Z5nodeID://b5472668592024-03-29T15:32:41.367645Z2nodeID://b5472669802024-03-29T15:32:41.367645Z2nodeID://b5472660982024-03-29T15:32:41.367645Z3nodeID://b5472662262024-03-29T15:32:41.367645Z3nodeID://b5472664922024-03-29T15:32:41.367645Z2nodeID://b5472666202024-03-29T15:32:41.367645Z2nodeID://b5472667652024-03-29T15:32:41.367645Z2nodeID://b5472658652024-03-29T15:32:41.367645Z15nodeID://b5472661322024-03-29T15:32:41.367645Z3nodeID://b5472662772024-03-29T15:32:41.367645Z2nodeID://b5472664052024-03-29T15:32:41.367645Z2nodeID://b5472661692024-03-29T15:32:41.367645Z3nodeID://b5472662902024-03-29T15:32:41.367645Z2nodeID://b5472669442024-03-29T15:32:41.367645Z2nodeID://b5472665632024-03-29T15:32:41.367645Z2nodeID://b5472663112024-03-29T15:32:41.367645Z2nodeID://b5472668362024-03-29T15:32:41.367645Z2nodeID://b5472659362024-03-29T15:32:41.367645Z6nodeID://b5472660752024-03-29T15:32:41.367645Z4nodeID://b5472662032024-03-29T15:32:41.367645Z3nodeID://b5472663482024-03-29T15:32:41.367645Z2nodeID://b5472667422024-03-29T15:32:41.367645Z2nodeID://b5472659872024-03-29T15:32:41.367645Z5nodeID://b5472668872024-03-29T15:32:41.367645Z2nodeID://b295389912024-03-29T15:32:41.367645ZVEGF is one such molecule>>39<<,40, and to test whether it was involved in tumor growth in MISTRG mice, we treated the mice with the human-VEGF inhibitor Avastin™.nodeID://b5472662542024-03-29T15:32:41.367645Z3nodeID://b5472663992024-03-29T15:32:41.367645Z2nodeID://b5472665272024-03-29T15:32:41.367645Z2nodeID://b5472667932024-03-29T15:32:41.367645Z2nodeID://b5472658932024-03-29T15:32:41.367645Z9nodeID://b5472660392024-03-29T15:32:41.367645Z4nodeID://b5472669212024-03-29T15:32:41.367645Z2nodeID://b5472661602024-03-29T15:32:41.367645Z3nodeID://b5472664332024-03-29T15:32:41.367645Z2nodeID://b5472665782024-03-29T15:32:41.367645Z2nodeID://b5472667062024-03-29T15:32:41.367645Z2nodeID://b5472665912024-03-29T15:32:41.367645Z2nodeID://b5472669722024-03-29T15:32:41.367645Z2nodeID://b5472662182024-03-29T15:32:41.367645Z3nodeID://b5472664842024-03-29T15:32:41.367645Z2nodeID://b5472666122024-03-29T15:32:41.367645Z2nodeID://b5472667572024-03-29T15:32:41.367645Z2nodeID://b5472658572024-03-29T15:32:41.367645Z19nodeID://b5472663762024-03-29T15:32:41.367645Z2nodeID://b5472666492024-03-29T15:32:41.367645Z2nodeID://b5472661242024-03-29T15:32:41.367645Z3nodeID://b5472658702024-03-29T15:32:41.367645Z13nodeID://b5472667702024-03-29T15:32:41.367645Z2nodeID://b5472660162024-03-29T15:32:41.367645Z4nodeID://b5472662822024-03-29T15:32:41.367645Z2nodeID://b5472664102024-03-29T15:32:41.367645Z2nodeID://b5472665552024-03-29T15:32:41.367645Z2nodeID://b5472668282024-03-29T15:32:41.367645Z2nodeID://b5472659282024-03-29T15:32:41.367645Z6nodeID://b5472660672024-03-29T15:32:41.367645Z4nodeID://b5472664612024-03-29T15:32:41.367645Z2nodeID://b5472667342024-03-29T15:32:41.367645Z2nodeID://b5472659792024-03-29T15:32:41.367645Z5nodeID://b5472668792024-03-29T15:32:41.367645Z2nodeID://b5472670012024-03-29T15:32:41.367645Z2nodeID://b5472661012024-03-29T15:32:41.367645Z3nodeID://b5472662462024-03-29T15:32:41.367645Z3nodeID://b295390012024-03-29T15:32:41.367645ZdiscussionnodeID://b5472665192024-03-29T15:32:41.367645Z2nodeID://b5472666402024-03-29T15:32:41.367645Z2nodeID://b5472667852024-03-29T15:32:41.367645Z2nodeID://b5472658852024-03-29T15:32:41.367645Z10nodeID://b5472669132024-03-29T15:32:41.367645Z2nodeID://b5472661522024-03-29T15:32:41.367645Z3nodeID://b5472662972024-03-29T15:32:41.367645Z2nodeID://b5472664252024-03-29T15:32:41.367645Z2nodeID://b5472661892024-03-29T15:32:41.367645Z3nodeID://b5472665832024-03-29T15:32:41.367645Z2nodeID://b5472663312024-03-29T15:32:41.367645Z2nodeID://b5472668562024-03-29T15:32:41.367645Z2nodeID://b5472659562024-03-29T15:32:41.367645Z5nodeID://b5472660952024-03-29T15:32:41.367645Z3nodeID://b5472662232024-03-29T15:32:41.367645Z3nodeID://b5472666042024-03-29T15:32:41.367645Z2nodeID://b5472663682024-03-29T15:32:41.367645Z2nodeID://b5472667622024-03-29T15:32:41.367645Z2nodeID://b5472658622024-03-29T15:32:41.367645Z16nodeID://b5472660082024-03-29T15:32:41.367645Z4nodeID://b295389932024-03-29T15:32:41.367645ZmethodsnodeID://b5472662742024-03-29T15:32:41.367645Z2nodeID://b5472664022024-03-29T15:32:41.367645Z2nodeID://b5472665472024-03-29T15:32:41.367645Z2nodeID://b5472669412024-03-29T15:32:41.367645Z2nodeID://b5472660592024-03-29T15:32:41.367645Z4nodeID://b5472661802024-03-29T15:32:41.367645Z3nodeID://b5472664532024-03-29T15:32:41.367645Z2nodeID://b5472665982024-03-29T15:32:41.367645Z2nodeID://b5472667262024-03-29T15:32:41.367645Z2nodeID://b5472669922024-03-29T15:32:41.367645Z2nodeID://b5472662382024-03-29T15:32:41.367645Z3nodeID://b5472668842024-03-29T15:32:41.367645Z2nodeID://b5472666322024-03-29T15:32:41.367645Z2nodeID://b5472663962024-03-29T15:32:41.367645Z2nodeID://b5472658772024-03-29T15:32:41.367645Z12nodeID://b5472667772024-03-29T15:32:41.367645Z2nodeID://b295389802024-03-29T15:32:41.367645ZEfficient development of human NK cells in existing humanized mouse models requires injection of exogenous human IL-15/IL-15Rα 7,>>12<<; because mouse IL-15/IL15Rα is not sufficient to support human NK cells in vivo.nodeID://b5472669052024-03-29T15:32:41.367645Z2nodeID://b5472666692024-03-29T15:32:41.367645Z2nodeID://b5472661442024-03-29T15:32:41.367645Z3nodeID://b5472667902024-03-29T15:32:41.367645Z2nodeID://b5472658902024-03-29T15:32:41.367645Z9nodeID://b5472660362024-03-29T15:32:41.367645Z4nodeID://b5472664172024-03-29T15:32:41.367645Z2nodeID://b5472663092024-03-29T15:32:41.367645Z2nodeID://b5472664302024-03-29T15:32:41.367645Z2nodeID://b5472659112024-03-29T15:32:41.367645Z7nodeID://b5472668112024-03-29T15:32:41.367645Z2nodeID://b5472665752024-03-29T15:32:41.367645Z2nodeID://b5472667032024-03-29T15:32:41.367645Z2nodeID://b5472659482024-03-29T15:32:41.367645Z5nodeID://b5472668482024-03-29T15:32:41.367645Z2nodeID://b5472660872024-03-29T15:32:41.367645Z3nodeID://b5472662152024-03-29T15:32:41.367645Z3nodeID://b5472664812024-03-29T15:32:41.367645Z2nodeID://b5472667542024-03-29T15:32:41.367645Z2nodeID://b5472658542024-03-29T15:32:41.367645Z21nodeID://b5472659992024-03-29T15:32:41.367645Z4nodeID://b5472668992024-03-29T15:32:41.367645Z2nodeID://b5472661212024-03-29T15:32:41.367645Z3nodeID://b5472662662024-03-29T15:32:41.367645Z2nodeID://b295390032024-03-29T15:32:41.367645Zthe study of low-proliferative, primary human hematopoietic malignancies, such as myelodysplastic syndromes or myeloproliferative neoplasia, that thus far have proven difficult to efficiently engraft [AR: OK] immunodeficient mice41,>>42<<.nodeID://b5472665392024-03-29T15:32:41.367645Z2nodeID://b5472666602024-03-29T15:32:41.367645Z2nodeID://b5472669332024-03-29T15:32:41.367645Z2nodeID://b5472661722024-03-29T15:32:41.367645Z3nodeID://b5472663002024-03-29T15:32:41.367645Z2nodeID://b5472664452024-03-29T15:32:41.367645Z2nodeID://b5472667182024-03-29T15:32:41.367645Z2nodeID://b5472659762024-03-29T15:32:41.367645Z5nodeID://b5472668762024-03-29T15:32:41.367645Z2nodeID://b5472663512024-03-29T15:32:41.367645Z2nodeID://b5472666242024-03-29T15:32:41.367645Z2nodeID://b5472662432024-03-29T15:32:41.367645Z3nodeID://b5472663882024-03-29T15:32:41.367645Z2nodeID://b5472665162024-03-29T15:32:41.367645Z2nodeID://b5472667822024-03-29T15:32:41.367645Z2nodeID://b5472658822024-03-29T15:32:41.367645Z11nodeID://b5472660282024-03-29T15:32:41.367645Z4nodeID://b5472669102024-03-29T15:32:41.367645Z2nodeID://b295389952024-03-29T15:32:41.367645ZHuman SIRPα expression was achieved by BAC-transgenesis in the same genetic background>>28<<. We intercrossed these strains by conventional breeding to obtain MITRG (M-CSFh/h IL-3/GM-CSFh/h TPOh/h Rag2-/- Il2rg-/-) and MISTRG (M-CSFh/h IL-3/GM-CSFh/h hSIRPAtg TPOh/h Rag2-/- Il2rg-/-) mice. We maintained them under specificnodeID://b5472662942024-03-29T15:32:41.367645Z2nodeID://b5472664222024-03-29T15:32:41.367645Z2nodeID://b5472665672024-03-29T15:32:41.367645Z2nodeID://b5472660792024-03-29T15:32:41.367645Z3nodeID://b5472669612024-03-29T15:32:41.367645Z2nodeID://b5472662072024-03-29T15:32:41.367645Z3nodeID://b5472664732024-03-29T15:32:41.367645Z2nodeID://b5472666012024-03-29T15:32:41.367645Z2nodeID://b5472667462024-03-29T15:32:41.367645Z2nodeID://b5472658462024-03-29T15:32:41.367645Z33nodeID://b5472661132024-03-29T15:32:41.367645Z3nodeID://b5472662582024-03-29T15:32:41.367645Z3nodeID://b5472666522024-03-29T15:32:41.367645Z2nodeID://b5472658972024-03-29T15:32:41.367645Z9nodeID://b5472667972024-03-29T15:32:41.367645Z2nodeID://b5472669252024-03-29T15:32:41.367645Z2nodeID://b295389822024-03-29T15:32:41.367645ZAs previously reported7,>>8<<,12, we observed very few human NK cells (hNKp46+hCD3-) in engrafted NSG mice (Fig.nodeID://b5472666892024-03-29T15:32:41.367645Z2nodeID://b5472661642024-03-29T15:32:41.367645Z3nodeID://b5472664372024-03-29T15:32:41.367645Z2nodeID://b5472660562024-03-29T15:32:41.367645Z4nodeID://b5472663292024-03-29T15:32:41.367645Z2nodeID://b5472664502024-03-29T15:32:41.367645Z2nodeID://b5472659312024-03-29T15:32:41.367645Z6nodeID://b5472665952024-03-29T15:32:41.367645Z2nodeID://b5472667232024-03-29T15:32:41.367645Z2nodeID://b5472659682024-03-29T15:32:41.367645Z5nodeID://b5472668682024-03-29T15:32:41.367645Z2nodeID://b5472662352024-03-29T15:32:41.367645Z3nodeID://b5472665082024-03-29T15:32:41.367645Z2nodeID://b5472667742024-03-29T15:32:41.367645Z2nodeID://b5472658742024-03-29T15:32:41.367645Z12nodeID://b5472669022024-03-29T15:32:41.367645Z2nodeID://b5472661412024-03-29T15:32:41.367645Z3nodeID://b5472662862024-03-29T15:32:41.367645Z2nodeID://b5472664142024-03-29T15:32:41.367645Z2nodeID://b295390052024-03-29T15:32:41.367645Zmonocyte-derived macrophages>>45<<, the trafficking of these cells in response to inflammation or infection, and the mechanisms of differentiation and effector function of M1 vs.nodeID://b5472665592024-03-29T15:32:41.367645Z2nodeID://b5472666802024-03-29T15:32:41.367645Z2nodeID://b5472669532024-03-29T15:32:41.367645Z2nodeID://b5472661922024-03-29T15:32:41.367645Z3nodeID://b5472663202024-03-29T15:32:41.367645Z2nodeID://b5472664652024-03-29T15:32:41.367645Z2nodeID://b5472667382024-03-29T15:32:41.367645Z2nodeID://b5472661052024-03-29T15:32:41.367645Z3nodeID://b5472670052024-03-29T15:32:41.367645Z2nodeID://b5472667512024-03-29T15:32:41.367645Z2nodeID://b5472659962024-03-29T15:32:41.367645Z4nodeID://b5472668962024-03-29T15:32:41.367645Z2nodeID://b5472666442024-03-29T15:32:41.367645Z2nodeID://b5472662632024-03-29T15:32:41.367645Z2nodeID://b5472660112024-03-29T15:32:41.367645Z4nodeID://b5472665362024-03-29T15:32:41.367645Z2nodeID://b5472669172024-03-29T15:32:41.367645Z2nodeID://b5472668092024-03-29T15:32:41.367645Z2nodeID://b5472660482024-03-29T15:32:41.367645Z4nodeID://b5472669302024-03-29T15:32:41.367645Z2nodeID://b295389972024-03-29T15:32:41.367645ZRecipient mice were engrafted with human hematopoietic stem and progenitor cells as previously described16-18,>>27<<,28. Briefly, human fetal liver samples were cut in small fragments, treated for 45 min at 37°C with Collagenase D (Roche, 100 ng/mL) and a cell suspension was prepared.nodeID://b5472664422024-03-29T15:32:41.367645Z2nodeID://b5472665872024-03-29T15:32:41.367645Z2nodeID://b5472667152024-03-29T15:32:41.367645Z2nodeID://b5472669812024-03-29T15:32:41.367645Z2nodeID://b5472660992024-03-29T15:32:41.367645Z3nodeID://b5472662272024-03-29T15:32:41.367645Z3nodeID://b5472664932024-03-29T15:32:41.367645Z2nodeID://b5472666212024-03-29T15:32:41.367645Z2nodeID://b5472667662024-03-29T15:32:41.367645Z2nodeID://b5472658662024-03-29T15:32:41.367645Z14nodeID://b5472661332024-03-29T15:32:41.367645Z3nodeID://b5472662782024-03-29T15:32:41.367645Z2nodeID://b5472664062024-03-29T15:32:41.367645Z2nodeID://b5472666722024-03-29T15:32:41.367645Z2nodeID://b5472662912024-03-29T15:32:41.367645Z2nodeID://b5472659002024-03-29T15:32:41.367645Z8nodeID://b5472668002024-03-29T15:32:41.367645Z2nodeID://b295389842024-03-29T15:32:41.367645ZWith the exception of the bone marrow, MITRG mice contained fewer human NK cells than MISTRG mice, most likely due to the previously reported requirement for human SIRPα for the survival of human NK cells in the periphery>>31<<. The hNKp46+hCD3- cells in MISTRG mice represented bona fide NK cells because like human NK cells they expressed the NK cell surface markers CD94, CD161, and killer inhibitory receptors (KIRs) (Supplementary Fig. 10a, b). Expression ofnodeID://b5472669452024-03-29T15:32:41.367645Z2nodeID://b5472661842024-03-29T15:32:41.367645Z3nodeID://b5472663122024-03-29T15:32:41.367645Z2nodeID://b5472660762024-03-29T15:32:41.367645Z4nodeID://b5472664572024-03-29T15:32:41.367645Z2nodeID://b5472663492024-03-29T15:32:41.367645Z2nodeID://b5472659512024-03-29T15:32:41.367645Z5nodeID://b5472664702024-03-29T15:32:41.367645Z2nodeID://b5472667432024-03-29T15:32:41.367645Z2nodeID://b5472659882024-03-29T15:32:41.367645Z5nodeID://b5472668882024-03-29T15:32:41.367645Z2nodeID://b5472661102024-03-29T15:32:41.367645Z3nodeID://b5472662552024-03-29T15:32:41.367645Z3nodeID://b5472665282024-03-29T15:32:41.367645Z2nodeID://b5472667942024-03-29T15:32:41.367645Z2nodeID://b5472658942024-03-29T15:32:41.367645Z9nodeID://b5472669222024-03-29T15:32:41.367645Z2nodeID://b5472661612024-03-29T15:32:41.367645Z3nodeID://b5472664342024-03-29T15:32:41.367645Z2nodeID://b295390072024-03-29T15:32:41.367645Zimmunity might be improved by a number of approaches, including expression of human MHC elements in mice or use of the bone marrow-liver-thymus (BLT) approach where human fetal tissues are transplanted along with human CD34+ cells>>48<<,49. The BLT approach results in more robust adaptive immune responses because T cells develop and are selected in a human thymic tissue.nodeID://b5472665792024-03-29T15:32:41.367645Z2nodeID://b5472667072024-03-29T15:32:41.367645Z2nodeID://b5472669732024-03-29T15:32:41.367645Z2nodeID://b5472662192024-03-29T15:32:41.367645Z3nodeID://b5472663402024-03-29T15:32:41.367645Z2nodeID://b5472664852024-03-29T15:32:41.367645Z2nodeID://b5472666132024-03-29T15:32:41.367645Z2nodeID://b5472667582024-03-29T15:32:41.367645Z2nodeID://b5472658582024-03-29T15:32:41.367645Z19nodeID://b5472661252024-03-29T15:32:41.367645Z3nodeID://b5472667712024-03-29T15:32:41.367645Z2nodeID://b5472666642024-03-29T15:32:41.367645Z2nodeID://b5472662832024-03-29T15:32:41.367645Z2nodeID://b5472660312024-03-29T15:32:41.367645Z4nodeID://b5472669372024-03-29T15:32:41.367645Z2nodeID://b5472665562024-03-29T15:32:41.367645Z2nodeID://b5472659292024-03-29T15:32:41.367645Z6nodeID://b5472663042024-03-29T15:32:41.367645Z2nodeID://b5472668292024-03-29T15:32:41.367645Z2nodeID://b5472660682024-03-29T15:32:41.367645Z4nodeID://b5472669502024-03-29T15:32:41.367645Z2nodeID://b295389992024-03-29T15:32:41.367645ZPhagocytic cells were depleted by intravenous retro-orbital injection of 100 μl of clodronate-loaded liposomes>>50<<. Clodronate-liposomes were injected 3 times daily and human NK cells in mouse liver were analyzed 24h after the last injection.nodeID://b5472664622024-03-29T15:32:41.367645Z2nodeID://b5472667352024-03-29T15:32:41.367645Z2nodeID://b5472661022024-03-29T15:32:41.367645Z3nodeID://b5472670022024-03-29T15:32:41.367645Z2nodeID://b5472662472024-03-29T15:32:41.367645Z3nodeID://b5472666412024-03-29T15:32:41.367645Z2nodeID://b5472667862024-03-29T15:32:41.367645Z2nodeID://b5472658862024-03-29T15:32:41.367645Z10nodeID://b5472669142024-03-29T15:32:41.367645Z2nodeID://b5472661532024-03-29T15:32:41.367645Z3nodeID://b5472662982024-03-29T15:32:41.367645Z2nodeID://b5472664262024-03-29T15:32:41.367645Z2nodeID://b5472666922024-03-29T15:32:41.367645Z2nodeID://b5472668202024-03-29T15:32:41.367645Z2nodeID://b5472659202024-03-29T15:32:41.367645Z7nodeID://b5472669652024-03-29T15:32:41.367645Z2nodeID://b295389862024-03-29T15:32:41.367645ZNK cells defend against pathogens by killing cells that lack surface MHC class I expression>>35<<, and by producing the IFN-γ 36.nodeID://b5472663322024-03-29T15:32:41.367645Z2nodeID://b5472664772024-03-29T15:32:41.367645Z2nodeID://b5472660962024-03-29T15:32:41.367645Z3nodeID://b5472666052024-03-29T15:32:41.367645Z2nodeID://b5472663692024-03-29T15:32:41.367645Z2nodeID://b5472659712024-03-29T15:32:41.367645Z5nodeID://b5472664902024-03-29T15:32:41.367645Z2nodeID://b5472661172024-03-29T15:32:41.367645Z3nodeID://b5472667632024-03-29T15:32:41.367645Z2nodeID://b5472658632024-03-29T15:32:41.367645Z15nodeID://b5472665112024-03-29T15:32:41.367645Z2nodeID://b5472661302024-03-29T15:32:41.367645Z3nodeID://b5472662752024-03-29T15:32:41.367645Z2nodeID://b5472664032024-03-29T15:32:41.367645Z2nodeID://b5472665482024-03-29T15:32:41.367645Z2nodeID://b5472669422024-03-29T15:32:41.367645Z2nodeID://b5472661812024-03-29T15:32:41.367645Z3nodeID://b5472664542024-03-29T15:32:41.367645Z2nodeID://b5472665992024-03-29T15:32:41.367645Z2nodeID://b5472667272024-03-29T15:32:41.367645Z2nodeID://b5472669932024-03-29T15:32:41.367645Z2nodeID://b5472662392024-03-29T15:32:41.367645Z3